Targeting a Poor Prognosis Marker for Tumor Therapy Summary The purpose of this proposal is to develop a medical treatment for the elimination of metastatic cancers. According to the National Cancer Institute, the survival rate for many types of cancer has improved in recent years;however, it is still the second leading cause of death in the United States. This proposal describes an experimental design to verify the suitability of basigin-2 (also known as CD147 or EMMPRIN) as a cell surface target for an innovative tumor therapy. This project will accomplish important goals in determining the suitability of basigin-2 for further drug development: 1) Provide proof of internalization of the target moiety (basigin-2) by using an antibody to basigin-2, and 2) Demonstrate that there is specificity, both in terms of greater ability to target the tumor over normal (lower level) expression and that anti-basigin is specific for the target. In this Phase I grant, a cytotoxin will be produced that has two components: 1) anti-basigin to specifically target and internalize into basigin-2 positive cells, and 2) a toxin that will inhibit protein synthesis upon internalization by the antibody. This innovative approach will create a molecule that targets tumor cells, metastasis and angiogenesis, with the idea to not just slow tumor cell proliferation, but to eliminate tumors. PUBLIC HEALTH RELEVANCE: Targeting a Poor Prognosis Marker for Tumor Therapy Narrative This project begins a new direction of potential treatment for a wide range of deadly cancers by targeting a molecule that is expressed on the surface of many tumor types with poor prognosis. While it is proposed to directly target these tumors through targeting the molecule, basigin-2, targeting of tumor metastasis and angiogenesis is also indicated, since basigin-2 plays important roles in those dangerous processes. The project builds on current technologies, but puts several together to go in a new, innovative direction.